scholarly journals Comprehensive Molecular Analysis of Mismatch Repair Gene Defects in Suspected Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Cases

2009 ◽  
Vol 69 (17) ◽  
pp. 7053-7061 ◽  
Author(s):  
James Mueller ◽  
Isabella Gazzoli ◽  
Prathap Bandipalliam ◽  
Judy E. Garber ◽  
Sapna Syngal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Molecular Analysis ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Hereditary Nonpolyposis ◽  
Gene Defects

Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer

2005 ◽  
Vol 23 (21) ◽  
pp. 4705-4712 ◽  
Author(s):  
Astrid T. Stormorken ◽  
Inger Marie Bowitz-Lothe ◽  
Tove Norèn ◽  
Elin Kure ◽  
Steinar Aase ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Predictive Values ◽  
Blood Samples ◽  
Bethesda Criteria ◽  
Amsterdam Criteria ◽  
Hereditary Nonpolyposis

Purpose Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. Patients and Methods Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. Results Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. Conclusion Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.

Genetic profiles of hereditary nonpolyposis colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 469-469
Author(s):  
C. Therklidsen ◽  
G. Jonsson ◽  
I. Bernstein ◽  
M. Nilbert
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Gene Mutations ◽  
Comparative Genomic ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Hereditary Nonpolyposis ◽  
Gains And Losses ◽  
Mismatch Repair Gene Mutations

469 Background: With the aim to identify genetic markers of hereditary nonpolyposis colorectal cancer (HNPCC), we applied tiling BAC array-based comparative genomic hybridization (aCGH) to 46 HNPCC-associated colorectal cancer. Methods: 32 k iling BAC arrays were used to generate high-density genomic profiles. Tumors were selected through a case-control design with half of the tumors derived from individuals with disease-predisposing mismatch repair gene mutations and the reminder from phenotypic HNPCC families without identified mutations. In addition, an equal number of sporadic tumors were used for comparison. Results: Tumors with disease-predisposing germline mutations showed frequent gains of chromosomes 1p (39%), 17 (43%), 19 (57%) and 22q (30%). HNPCC associated tumors without mutations did as a group have more complex alterations with the most frequent changes being gains of 20q (70%), 19 (35%), 17 (26%) and loss of 18 (39%). Gains of 1p and 20q and loss of chromosome 18 were identified as significant discriminators between HNPCC tumors with/without germline MMR gene mutations. Conclusions: The aCGH profiles of HNPCC-associated colorectal cancer suggest that specific gains and losses may be used to distinguish between tumors with/without germline mismatch repair gene mutations. No significant financial relationships to disclose.

Immunohistochemistry detects mismatch repair gene defects in colorectal cancer

2006 ◽  
Vol 8 (5) ◽  
pp. 411-417 ◽  
Author(s):  
F. Hameed ◽  
P. A. Goldberg ◽  
P. Hall ◽  
U. Algar ◽  
R. van Wijk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Gene Defects

scholarly journals Deficient DNA mismatch repair and persistence of SARS-CoV-2 RNA shedding: a case report of hereditary nonpolyposis colorectal cancer with COVID-19 infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Farzana Haque ◽  
Patrick Lillie ◽  
Farhana Haque ◽  
Anthony Maraveyas
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Rna Virus ◽  
Genetic Mutation ◽  
Host Cells ◽  
Nasopharyngeal Swab ◽  
Viral Shedding ◽  
Hereditary Nonpolyposis

Abstract Background Several independent risk factors have been reported to influence viral shedding following COVID-19 infection, but the influence of host-related molecular factors has not yet been described. We report a case of a cancer patient with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) who manifested SARS-CoV-2 PCR (polymerase chain reaction) positivity for at least 54 days after contracting mild COVID-19 illness. We propose that deficient mismatch repair (MMR) may play a role in the prolonged SARS-CoV-2 RNA shedding. Case presentation A patient with Lynch syndrome was under surveillance for metastatic adenocarcinoma after completing palliative chemotherapy in October 2019. Between the period of April 2020 to June 2020, he was admitted multiple times to address several clinical needs mainly related to his underlying malignancy. These included progressive disease observed in the aortocaval lymph nodes leading to recurrent episodes of upper gastrointestinal bleeding, dehydration resulting in acute kidney injury and a short-lived episode of pyrexia. A SARS-CoV-2 PCR of the nasopharyngeal swab (NPS) was positive at his initial admission with mild COVID-19 symptoms. He remained positive on subsequent admissions when tested routinely for SARS-CoV-2 without demonstrating any apparent clinical features of COVID-19 infection. The MMR pathway, a component of DNA damage response (DDR), is impaired in Lynch syndrome due to an inherited genetic mutation. This pathway is also required for viral clearance from the host cells following certain RNA viral infections like influenza virus and other coronaviridae. Here we provide a current understanding of the importance of DDR deficiencies in the clearance of RNA virus and suggest how this may play a similar role in the clearance of COVID-19, as evident in our case that demonstrated persistent positivity. Conclusion The importance of understanding the scientific basis of extended viral shedding during the COVID-19 pandemic is now centre-stage in the establishment of robust track and trace services to allow the recovery and function of societies and economies. This patient with Lynch syndrome recovered from infection but had prolonged viral positivity, which might merit further investigation to better understand the effect of this condition on infection duration and outcome.

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